Babesiosis is caused by intraerythrocytic protozoan parasites transmitted by ticks and affects a wide range of domestic and wild animals and occasionally humans. The current study aimed to investigate the effect of B. divergens infected erythrocytes on spleen histopathology, cell cycle alteration, and the presence of oxidative stress. Mongolian gerbils were challenged with 5 × 10(6) Babesia divergens infected erythrocytes. Parasitemia reached approximately 77% at day 5 postinfection. Infection also induced injury of the spleen. This was evidenced with (i) increases in cellular damage of the spleen, (ii) decrease in antioxidant capacity as indicated by decreased glutathione, catalase, and superoxide dismutase levels, (iii) increased production of malondialdehyde and nitric oxide derived products (nitrite/nitrate), and (iv) increased lactic acid dehydrogenase activity and protein carbonyl content in the spleen. Infection interfered with normal cell cycle of the spleen cells at G0/G1, S, and G2/M phases. On the basis of the above results it can be hypothesized that B. divergens infected erythrocytes could alter the spleen histopathology and cause cell cycle alteration and induce oxidative stress in splenic tissue.